More than 15 distinct transforming genes have been identified in the genomes of oncogenic retroviruses. Each of these oncogenes has a homologue in the chromosomal DNA of all vertebrate species. Current evidence indicates that this highly conserved set of genes may play a vital role in cell proliferation and/or differentiation. In addition, inappropriate expression of some of these genes has been implicated in the genesis of cancer. Our efforts have been concentrated on the cellular homologue of the ras gene, the oncogene carried by Harvey and Kirstein Sarcoma viruses. An amplified expression of the cellular ras gene has been correlated with the oncogenesis of human bladder, lung and colon carcinomas. In this study we are investigating the role of ras gene expression in the induction of rat and human mammary carcinomas. It is our hypothesis that mammary cancer can be triggered by activation of ras gene expression. Enhanced expression might result from genetic changes at the ras locus itself such as a rearrangement involving new promoter sequences, or from changes at other, so-called "regulatory" loci. The expression of the ras gene will be determined in growing vs regressing mammary tumors, hormone-dependent vs hormone-independent tumors, and the mammary gland of rodents during normal development or chemical or viral carcinogenesis. The ras gene expression will be also determined in hyperplastic alveolar nodules, benign and malignant breast diseases of humans. The goal of this proposal is to provide us a fundamental basis for better understanding the mechanisms by which oncogenes involved in neoplastic growth.